ABSTRACT Chikungunya virus (CHIKV) is an alphavirus spread by mosquitos that causes persistent arthritis in approximately one-fourth of patients. There is currently no evidence-based standard treatment for CHIKV chronic arthritis. In the current proposal, we seek to identify a therapeutic target for relapsing-remitting arthritis associated with CHIKV infection. Our Colombian cohort (n = 500) of patients affected by CHIKV affords a unique opportunity to further understand the immunology of CHIKV arthritis flares. Our preliminary data suggest that alteration of regulatory T cell (Treg) function may play a role in CHIKV arthritis pathogenesis. Novel low-dose interleukin-2 (IL-2) based therapies for autoimmune disease have been shown to up-regulate Tregs and may be of use in CHIKV arthritis flares. Our main goal is to further understand the role of IL-2 in Treg populations in CHIKV arthritis. Our central hypothesis is that chronic CHIKV arthritis activity is associated with deficient IL-2 mediated Treg levels and low-dose IL-2 is a potential therapeutic. This hypothesis will be evaluated in two specific aims. In Aim 1, we will describe the role of IL-2 in Treg expansion and corresponding arthritis severity during CHIKV arthritis flare vs. remission compared to non-arthritic controls. In Aim 2, we will determine the role of IL-2 therapy in the treatment of CHIKV arthritis in a mouse model. The impact of this research will determine the correlation between Tregs and CHIKV-associated arthralgia. It may provide a pre-clinical evaluation of low-dose IL-2 therapy for CHIKV arthritis and insights into the use of this novel therapeutic for viral arthritis in general.